Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

Jason E. Farrar, Paola Quarello, Ross Fisher, Kelly A. O'Brien, Anna Aspesi, Sara Parrella, Adrianna L. Henson, Nancy E. Seidel, Eva Atsidaftos, Supraja Prakash, Shahla Bari, Emanuela Garelli, Robert J. Arceci, Irma Dianzani, Ugo Ramenghi, Adrianna Vlachos, Jeffrey M. Lipton, David M. Bodine, Steven R. Ellis

Research output: Contribution to journalArticle

Abstract

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene.

Original languageEnglish (US)
Pages (from-to)985-991
Number of pages7
JournalAmerican Journal of Hematology
Volume89
Issue number10
DOIs
StatePublished - Oct 1 2014
Externally publishedYes

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Diamond-Blackfan Anemia
RNA Precursors
Genetic Association Studies
Eukaryotic Large Ribosome Subunits
Ribosomal Proteins
Eukaryotic Small Ribosome Subunits
Genes
Capillary Electrophoresis
Anemia
Mutation

ASJC Scopus subject areas

  • Hematology

Cite this

Farrar, J. E., Quarello, P., Fisher, R., O'Brien, K. A., Aspesi, A., Parrella, S., ... Ellis, S. R. (2014). Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. American Journal of Hematology, 89(10), 985-991. https://doi.org/10.1002/ajh.23807

Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. / Farrar, Jason E.; Quarello, Paola; Fisher, Ross; O'Brien, Kelly A.; Aspesi, Anna; Parrella, Sara; Henson, Adrianna L.; Seidel, Nancy E.; Atsidaftos, Eva; Prakash, Supraja; Bari, Shahla; Garelli, Emanuela; Arceci, Robert J.; Dianzani, Irma; Ramenghi, Ugo; Vlachos, Adrianna; Lipton, Jeffrey M.; Bodine, David M.; Ellis, Steven R.

In: American Journal of Hematology, Vol. 89, No. 10, 01.10.2014, p. 985-991.

Research output: Contribution to journalArticle

Farrar, JE, Quarello, P, Fisher, R, O'Brien, KA, Aspesi, A, Parrella, S, Henson, AL, Seidel, NE, Atsidaftos, E, Prakash, S, Bari, S, Garelli, E, Arceci, RJ, Dianzani, I, Ramenghi, U, Vlachos, A, Lipton, JM, Bodine, DM & Ellis, SR 2014, 'Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis', American Journal of Hematology, vol. 89, no. 10, pp. 985-991. https://doi.org/10.1002/ajh.23807
Farrar JE, Quarello P, Fisher R, O'Brien KA, Aspesi A, Parrella S et al. Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. American Journal of Hematology. 2014 Oct 1;89(10):985-991. https://doi.org/10.1002/ajh.23807
Farrar, Jason E. ; Quarello, Paola ; Fisher, Ross ; O'Brien, Kelly A. ; Aspesi, Anna ; Parrella, Sara ; Henson, Adrianna L. ; Seidel, Nancy E. ; Atsidaftos, Eva ; Prakash, Supraja ; Bari, Shahla ; Garelli, Emanuela ; Arceci, Robert J. ; Dianzani, Irma ; Ramenghi, Ugo ; Vlachos, Adrianna ; Lipton, Jeffrey M. ; Bodine, David M. ; Ellis, Steven R. / Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis. In: American Journal of Hematology. 2014 ; Vol. 89, No. 10. pp. 985-991.
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